The major objectives of these studies are to attempt to determine: (1) the route of metabolism of the thiono-sulfur moiety in various chemical groups such as a thioamide, thioureas, thiouracils, thioimidazole phosphorothionates and carbon disulfide; (2) the abiblity of these various thiono-sulfur containing compounds to produce liver damage; (3) the ability of these thiono-sulfur containing compounds to decrease the level of hepatic cytochrome P-450 and inhibit monooxygenase activity when administered in vivo or incubated with hepatic microsomes in vitro; (4) the nature of the covalent bond(s) formed between the sulfur atom released in the metabolism of some of these compounds and the amino acids of cytochrome P-450; (5) the structure of the products formed in the covalent binding of the carbon and phosphorus-containing portions of parathion and the carbon containing portions of carbon disulfide and thioacetamide to the proteins of hepatic microsomes; (6) the mechanism by which the metabolism of thiono-sulfur containing compounds leads to inhibition of the cytochrome P-450 containing monooxygenases and liver necrosis.